A subset of CD4/CD8 double-negative T cells expresses HIV proteins in patients on antiretroviral therapy

Laura K. DeMaster, Xiaohe Liu, D. Jake VanBelzen, Benjamin Trinité, Lingjie Zheng, Luis M. Agosto, Stephen A. Migueles, Mark Connors, Lidia Sambucetti, David N. Levy, Alexander O. Pasternak, Una O'Doherty

Research output: Contribution to journalArticle

Abstract

A major goal in HIV eradication research is characterizing the reservoir cells that harbor HIV in the presence of antiretroviral therapy (ART), which reseed viremia after treatment is stopped. In general, it is assumed that the reservoir consists of CD4+ T cells that express no viral proteins. However, recent findings suggest that this may be an overly simplistic view and that the cells that contribute to the reservoir may be a diverse population that includes both CD4+ and CD4- cells. In this study, we directly infected resting CD4+ T cells and used fluorescence-activated cell sorting (FACS) and fiber-optic array scanning technology (FAST) to identify and image cells expressing HIV Gag. We found that Gag expression from integrated proviruses occurred in resting cells that lacked surface CD4, likely resulting from Nef- and Env-mediated receptor internalization. We also extended our approach to detect cells expressing HIV proteins in patients suppressed on ART. We found evidence that rare Gag+ cells persist during ART and that these cells are often negative for CD4. We propose that these double-negative α/β T cells that express HIV protein may be a component of the long-lived reservoir.

Original languageEnglish (US)
Pages (from-to)2165-2179
Number of pages15
JournalJournal of virology
Volume90
Issue number5
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    DeMaster, L. K., Liu, X., VanBelzen, D. J., Trinité, B., Zheng, L., Agosto, L. M., Migueles, S. A., Connors, M., Sambucetti, L., Levy, D. N., Pasternak, A. O., & O'Doherty, U. (2016). A subset of CD4/CD8 double-negative T cells expresses HIV proteins in patients on antiretroviral therapy. Journal of virology, 90(5), 2165-2179. https://doi.org/10.1128/JVI.01913-15